tbuckley/cabot-search huggingface dataset:
STRling: a k-mer counting approach that detects short tandem repeat expansions at known and novel loci
Authors: Harriet Dashnow, Brent S. Pedersen, Laurel Hiatt, Joe Brown, Sarah J. Beecroft, Gianina Ravenscroft, Amy J. LaCroix, Phillipa Lamont, Richard H. Roxburgh, Miriam J. Rodrigues, Mark Davis, Heather C. Mefford, Nigel G. Laing, Aaron R. Quinlan
Journal: Genome biology (2022)

Expansions of short tandem repeats (STRs) cause many rare diseases. Expansion detection is challenging with short-read DNA sequencing data since supporting reads are often mapped incorrectly. Detection is particularly difficult for "novel" STRs, which include new motifs at known loci or STRs absent from the reference genome. We developed STRling to efficiently count k-mers to recover informative reads and call expansions at known and novel STR loci. STRling is sensitive to known STR disease loci, has a low false discovery rate, and resolves novel STR expansions to base-pair position accuracy. It is fast, scalable, open-source, and available at: github.com/quinlan-lab/STRling .
Fundamental Pathobiology of Coronary Atherosclerosis and Clinical Implications for Chronic Ischemic Heart Disease Management—The Plaque Hypothesis
Authors: Peter H. Stone, Peter Libby, William E. Boden
Journal: JAMA Cardiology (2022)

Recent clinical and imaging studies underscore that major adverse cardiac events (MACE) outcomes are associated not solely with severe coronary obstructions (ischemia hypothesis or stenosis hypothesis), but with the plaque burden along the entire coronary tree. New research clarifies the pathobiologic mechanisms responsible for plaque development/progression/destabilization leading to MACE (plaque hypothesis), but the translation of these insights to clinical management strategies has lagged. This narrative review elaborates the plaque hypothesis and explicates the current understanding of underlying pathobiologic mechanisms, the provocative destabilizing influences, the diagnostic and therapeutic implications, and their actionable clinical management approaches to optimize the management of patients with chronic coronary disease.
Automating Hair Loss Labels for Universally Scoring Alopecia From Images
Authors: Cameron Gudobba, Tejas Mane, Aylar Bayramova, Natalia Rodriguez, Leslie Castelo-Soccio, Temitayo A. Ogunleye, Susan C. Taylor, George Cotsarelis, Elena Bernardis
Journal: JAMA Dermatology (2022)

Clinical estimation of hair density has an important role in assessing and tracking the severity and progression of alopecia, yet to the authors' knowledge, no automation currently exists for this process. While some algorithms have been developed to assess alopecia presence on a binary level, their scope has been limited by focusing on a re-creation of the Severity of Alopecia Tool (SALT) score for alopecia areata (AA). Yet hair density loss is common to all alopecia forms, and an evaluation of that loss is used in established scoring systems for androgenetic alopecia (AGA), central centrifugal cicatricial alopecia (CCCA), and many more.
Discovery and identification of EIF2AK2 as a direct key target of berberine for anti-inflammatory effects
Authors: Wei Wei, Qingxuan Zeng, Yan Wang, Xixi Guo, Tianyun Fan, Yinghong Li, Hongbin Deng, Liping Zhao, Xintong Zhang, Yonghua Liu, Yulong Shi, Jingyang Zhu, Xican Ma, Yanxiang Wang, Jiandong Jiang, Danqing Song
Journal: Acta Pharmaceutica Sinica B (2022)

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.
Application of Deep Learning on Single-Cell RNA Sequencing Data Analysis: A Review
Authors: Matthew Brendel, Chang Su, Zilong Bai, Hao Zhang, Olivier Elemento, Fei Wang
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Single-cell RNA sequencing (scRNA-seq) has become a routinely used technique to quantify the gene expression profile of thousands of single cells simultaneously. Analysis of scRNA-seq data plays an important role in the study of cell states and phenotypes, and has helped elucidate biological processes, such as those occurring during the development of complex organisms, and improved our understanding of disease states, such as cancer, diabetes, and coronavirus disease 2019 (COVID-19). Deep learning, a recent advance of artificial intelligence that has been used to address many problems involving large datasets, has also emerged as a promising tool for scRNA-seq data analysis, as it has a capacity to extract informative and compact features from noisy, heterogeneous, and high-dimensional scRNA-seq data to improve downstream analysis. The present review aims at surveying recently developed deep learning techniques in scRNA-seq data analysis, identifying key steps within the scRNA-seq data analysis pipeline that have been advanced by deep learning, and explaining the benefits of deep learning over more conventional analytic tools. Finally, we summarize the challenges in current deep learning approaches faced within scRNA-seq data and discuss potential directions for improvements in deep learning algorithms for scRNA-seq data analysis.
JAMA Cardiology
Authors: Patrick O'gara, Marc Sabatine, Clyde Boston, Ann Yancy, Michael Pencina, Carolina North, Robert Harrington, Adrian Hernandez, Mhs Durham, North Carolina, Ajay Kirtane, New York, Roxana Mehran, Pradeep Natarajan, Kristen Boston, Seattle Patton, Washington Udelson, Sadiya Khan, Gregg Fonarow, Los Angeles, Sharlene Day, Laine Thomas, Akhil Narang, Julia Getts, Eugene Braunwald, Judith Hochman, Donald Lloyd-Jones, Scm Chicago, Michael Parmacek, Daniel Simon, Sidney Smith, Chapel Hill, Carolina Douglas, E Vaughan, Myron Weisfeldt, Maryland Douglas, P Zipes, Paul Armstrong, Shinya Goto, Peter Liu, Renato Lopes, Carolina Prabhakaran, Hugh Watkins, Harvey White, Habib Yacoub, Frs London, Gregory Curfman, Annette Flanagin, Michael Berkwits, Brenda Gregoline, Tracy Frey, Iris Lo, Kevin Brown, Bernadette Hromin, Erin Keenan, Rebecca Langley, Kris Simmons, Connie Manno, Sara Billings, Doug Brandt, Timothy Gray, Peter Olson, Juliet Orellana, Paul Ruich, Kirby Snell, Judith Ahlers, Stephanie Beckmeyer, Dawn Bielawski, Jane Calayag, Jan Clavey, Mary Coerver-Connolly, Amy Eutsey, Paul Jaworski, Ruth Kaufman, Laura King, Martha Lentz, Jenny Mackay, Nellie Mcgrew, Charon Pierson, Lori Ryan, Thressa Smith, Divya Sreekumar, Donna Thordsen, Christine Tilles, Emma Underdown, Cara Wallace, Becki Weiss, Christina West, Caroline Woods, Erin Kato, Jacob Kendall-Taylor, Monica Mungle, Lenette Gardner-Gullens, Fanny Brown, Anna Bukowski, Lee Calibeo, Jordan Faber, Andrew Given, Tosca Hall, Kenneth Otani, Caroline Sietmann, Angelia Waltower, Jesse Mcquarters, Elena Guobyte, Daniel Morrow, Shelly Steff, Jim Michalski, Eman Aly, Reuben Rios, Mary Ferkaluk, Jonathan Laxamana, Sidra Bonner, Heather Hsu, Andrew Ibrahim, Karen Bucher, Andy Rekito, Nick Reback, Lohitha Kethu, Marla Erson, Joseph Thornton, Thomas Easley, Brian Shields, Karen Adams-Taylor, Paul Gee, Anna Frazier, Monica Smith, Julie Burton, Ronna Hewitt, Mary Sieck, Geneine Someren, Jamaal Vargas, Content Systems, Mike Bujewski, Nathan Mitre, Digital Production, Regina Brownlee, Amanda Camino, Brenda Chandler-Grayer, Emily Dunn, Amy Evers, Maleeka Holden, Teri Hutchison, Dan Knowles, Joshua Lampinen, Natalie Marsh, Patricia Panek, Marla Seidell, La Son, Diggs Sledge, Julian Graphics, Joe Amft, Jonathan Chala, Maria Duda, Fred Furtner, Carolyn Hall, Maria Kowalkowski, Joy Farrell, Maria Giannini, Sasha Grossman, Kate Lander, Judith Literskis, Teresa Omiotek, Michael Ryder, James Madara, Kirsten Bibbins-Domingo, Robert Bonow
Journal: JAMA Cardiology (2022)

science, and evidence-based health policy.Health equity, especially when supported by original science, is a leading editorial priority.
Maternal Metals Exposure and Infant Weight Trajectory: The Japan Environment and Children’s Study (JECS)
Authors: Yu Taniguchi, Shin Yamazaki, Shoji F. Nakayama, Makiko Sekiyama, Takehiro Michikawa, Tomohiko Isobe, Miyuki Iwai-Shimada, Yayoi Kobayashi, Hiroshi Nitta, Mari Oba, Michihiro Kamijima
Journal: Environmental Health Perspectives (2022)

Background: To our knowledge, the association of maternal exposure to metallic elements with weight trajectory pattern from the neonatal period has not been investigated. Objectives: The goals of this study were to identify infant growth trajectories in weight in the first 3 y of life and to determine the associations of maternal blood levels of lead, cadmium, mercury, selenium, and manganese with growth trajectory. Methods: This longitudinal study, part of the Japan Environment and Children Study, enrolled 103,099 pregnant women at 15 Regional Centres across Japan between 2011 and 2014. Lead, cadmium, mercury, selenium, and manganese levels were measured in blood samples collected in the second (14–27 wk gestational age) or third trimester (≥28wk). Growth trajectory of 99,014 children was followed until age 3 y. Raw weight values were transformed to age- and sex-specific weight standard deviation (SD) scores, and latent-class group-based trajectory models were estimated to determine weight trajectories. Associations between maternal metallic element levels and weight trajectory were examined using multinomial logistic regression models after confounder adjustment. Results: We identified 5 trajectory patterns based on weight SD score: 4.74% of infants were classified in Group I, very small to small; 31.26% in Group II, moderately small; 21.91% in Group III, moderately small to moderately large; 28.06% in Group IV, moderately large to normal; and 14.03% in Group V, moderately large to large. On multinomial logistic regression, higher maternal lead and selenium levels tended to be associated with increased odds ratios (ORs) of poor weight SD score trajectories (Groups I and II), in comparison with Group III. Higher levels of mercury were associated with decreased ORs, whereas higher levels of manganese were associated with increased ORs of "moderately large" trajectories (Groups IV and V). Discussion: Maternal lead, mercury, selenium, and manganese blood levels affect infant growth trajectory pattern in the first 3 y of life. https://doi.org/10.1289/EHP10321
Erratum: “Examining the Relationship between Climate Change and Vibriosis in the United States: Projected Health and Economic Impacts for the 21st Century”
Authors: Megan Sheahan, Caitlin A. Gould, James E. Neumann, Patrick L. Kinney, Sandra Hoffmann, Charles Fant, Xinyue Wang, Michael Kolian
Journal: Environmental Health Perspectives (2022)
Crucial roles of circulating tumor cells in the metastatic cascade and tumor immune escape: biology and clinical translation
Authors: Klaus Pantel, Catherine Alix-Panabières
Journal: Journal for ImmunoTherapy of Cancer (2022)

Cancer-related deaths are mainly caused by metastatic spread of tumor cells from the primary lesion to distant sites via the blood circulation. Understanding the mechanisms of blood-borne tumor cell dissemination by the detection and molecular characterization of circulating tumor cells (CTCs) in the blood of patients with cancer has opened a new avenue in cancer research. Recent technical advances have enabled a comprehensive analysis of the CTCs at the genome, transcriptome and protein level as well as first functional studies using patient-derived CTC cell lines. In this review, we describe and discuss how research on CTCs has yielded important insights into the biology of cancer metastasis and the response of patients with cancer to therapies directed against metastatic cells. Future investigations will show whether CTCs leaving their primary site are more vulnerable to attacks by immune effector cells and whether cancer cell dissemination might be the 'Achilles heel' of metastatic progression. Here, we focus on the lessons learned from CTC research on the biology of cancer metastasis in patients with particular emphasis on the interactions of CTCs with the immune system. Moreover, we describe and discuss briefly the potential and challenges for implementing CTCs into clinical decision-making including detection of minimal residual disease, monitoring efficacies of systemic therapies and identification of therapeutic targets and resistance mechanisms.
Erratum to “Efficacy and Safety of Darolutamide in Patients with Nonmetastatic Castration-resistant Prostate Cancer Stratified by Prostate-specific Antigen Doubling Time: Planned Subgroup Analysis of the Phase 3 ARAMIS Trial” [Eur Urol 2022]
Authors: Martin Bögemann, Neal D. Shore, Matthew R. Smith, Teuvo L.J. Tammela, Albertas Ulys, Egils Vjaters, Sergey Polyakov, Mindaugas Jievaltas, Murilo Luz, Boris Alekseev, Thierry Lebret, Martin Schostak, Frank Verholen, Marie-Aude Le Berre, Shankar Srinivasan, Jorge Ortiz, Ateesha F. Mohamed, Toni Sarapohja, Karim Fizazi
Journal: European Urology (2022)
Smartphone accelerometer data as a proxy for clinical data in modeling of bipolar disorder symptom trajectory
Authors: Casey C. Bennett, Mindy K. Ross, EuGene Baek, Dohyeon Kim, Alex D. Leow
Journal: npj Digital Medicine (2022)

Being able to track and predict fluctuations in symptoms of mental health disorders such as bipolar disorder outside the clinic walls is critical for expanding access to care for the global population. To that end, we analyze a dataset of 291 individuals from a smartphone app targeted at bipolar disorder, which contains rich details about their smartphone interactions (including typing dynamics and accelerometer motion) collected everyday over several months, along with more traditional clinical features. The aim is to evaluate whether smartphone accelerometer data could serve as a proxy for traditional clinical data, either by itself or in combination with typing dynamics. Results show that accelerometer data improves the predictive performance of machine learning models by nearly 5% over those previously reported in the literature based only on clinical data and typing dynamics. This suggests it is possible to elicit essentially the same "information" about bipolar symptomology using different data sources, in a variety of settings.
Progressive pulmonary fibrosis: an expert group consensus statement
Authors: Sujeet K. Rajan, Vincent Cottin, Raja Dhar, Sonye Danoff, Kevin R. Flaherty, Kevin K. Brown, Anant Mohan, Elizabeth Renzoni, Murali Mohan, Zarir Udwadia, Padmanabha Shenoy, David Currow, Anand Devraj, Bhavin Jankharia, Ritu Kulshrestha, Steve Jones, Claudia Ravaglia, Silvia Quadrelli, Rajam Iyer, Sahajal Dhooria, Martin Kolb, Athol U. Wells
Journal: European Respiratory Journal (2022)

This expert group consensus statement emphasises the need for standardising the definition of progressive fibrosing interstitial lung diseases (F-ILDs), with an accurate initial diagnosis being of paramount importance in ensuring appropriate initial management. Equally, case-by-case decisions on monitoring and management are essential, given the varying presentations of F-ILDs and the varying rates of progression. The value of diagnostic tests in risk stratification at presentation and, separately, the importance of a logical monitoring strategy, tailored to manage the risk of progression, are also stressed. The term “progressive pulmonary fibrosis” (PPF) exactly describes the entity that clinicians often face in practice. The importance of using antifibrotic therapy early in PPF (once initial management has failed to prevent progression) is increasingly supported by evidence. Artificial intelligence software for high-resolution computed tomography analysis, although an exciting tool for the future, awaits validation. Guidance is provided on pulmonary rehabilitation, oxygen and the use of non-invasive ventilation focused specifically on the needs of ILD patients with progressive disease. PPF should be differentiated from acute deterioration due to drug-induced lung toxicity or other forms of acute exacerbations. Referral criteria for a lung transplant are discussed and applied to patient needs in severe diseases where transplantation is not realistic, either due to access limitations or transplantation contraindications. In conclusion, expert group consensus guidance is provided on the diagnosis, treatment and monitoring of F-ILDs with specific focus on the recognition of PPF and the management of pulmonary fibrosis progressing despite initial management.
Psychotropic Medication Use and Psychiatric Disorders During the COVID-19 Pandemic Among Danish Children, Adolescents, and Young Adults
Authors: Mette Bliddal, Lotte Rasmussen, Jacob Harbo Andersen, Peter Bjødstrup Jensen, Anton Pottegård, Trine Munk-Olsen, Helene Kildegaard, Rikke Wesselhoeft
Journal: JAMA Psychiatry (2022)

The direct and indirect implications of the COVID-19 pandemic have been associated with the mental health of children and adolescents, but it is uncertain whether these implications have been associated with changes in prescribing and diagnosis patterns.To examine psychotropic medication use and rates of psychiatric disorders in Danish children, adolescents, and young adults during the COVID-19 pandemic.This population-based, descriptive register-based cohort study included all Danish individuals aged 5 to 24 years from January 1, 2017, until June 30, 2022.Rates of filled prescriptions of psychotropic medications, including antipsychotics, anxiolytics, hypnotics, sedatives, antidepressants, and psychostimulants, and all inpatient and outpatient contacts with mental and behavioral disorders. Rates of new (incident) and total (prevalent) psychotropic medication use and psychiatric diagnoses were estimated. Rate ratios (RRs) were assessed between observed and expected numbers of incident psychotropic medication use or psychiatric diagnoses from March 2020 to June 30, 2022, comparing observed numbers with expected numbers predicted from the modeled prepandemic trend.The study identified 108 840 (58 856 female individuals [54%]; median [IQR] age, 18 [14-22] years) incident psychotropic medication users. From March 2020 (first national lockdown) to June 2022, the rate of incident users of any psychotropic medication showed a relative increase of 18% (RR, 1.18; CI, 1.17-1.20) compared with expected numbers, which was primarily associated with an increase among those aged 12 to 17 years of 37% (RR, 1.37; 95% CI, 1.34-1.41). Similarly, there was an overall relative increase of incident psychiatric disorders of 5% (incidence rate, 1.05; CI, 1.04-1.07) (incident cases, 114 048 [58 708 female individuals (51%)]), which was associated with an increase in hyperkinetic disorders (RR, 1.13; CI, 1.09-1.18) and anxiety disorders (RR, 1.04; CI, 1.02-1.06). Prevalence patterns showed similar trends of an overall increase in psychotropic medication use and psychiatric disorders. One of 3 new users of an individual drug group had filled a prescription for a drug from another psychotropic medication group within the prior 6 months.The results of this cohort study suggest that Danish youths experienced an increase in rates of psychotropic treatment and psychiatric disorder diagnoses during the COVID-19 pandemic, which was most pronounced among those aged 12 to 17 years. The increase was observed for children and adolescents with and without a psychiatric history within the last 5 years.
Inflammasome activation mediated by oxidised low-density lipoprotein in patients with sleep apnoea and early subclinical atherosclerosis
Authors: Elena Díaz-García, David Sanz-Rubio, Sara García-Tovar, Enrique Alfaro, Pablo Cubero, Ana V. Gil, José M. Marin, Carolina Cubillos-Zapata, Francisco García-Río
Journal: European Respiratory Journal (2022)

Background Atherosclerosis is a common comorbidity of obstructive sleep apnoea (OSA) patients, caused by the interaction of dyslipidaemia and systemic inflammation. The OSA pro-inflammatory response is mediated by NLRP3 inflammasome activation, which requires a priming signal mediated by intermittent hypoxia (IH) and an activation signal provided by soluble stimulus present in plasma. Our objectives were to study oxidised low-density lipoprotein (oxLDL) expression in OSA patients with or without early subclinical atherosclerosis (eSA) as well as its contribution to NLRP3 activation and tissue factor (TF) release. Methods We analysed oxLDL, key components of the NLRP3 inflammasome cascade and TF in plasma and monocytes from OSA patients and non-apnoeic subjects, with or without eSA as determined by increased carotid intima–media thickness without the appearance of atherosclerotic plaques. The oxLDL contribution to NLRP3 inflammasome activation was assessed using in vitro models. Results High levels of oxLDL were identified in plasma from OSA patients, particularly in those with eSA, as well as an overexpression of NLRP3 cascade components and TF. Furthermore, in vitro models showed that both oxLDL and plasma from OSA patients with eSA act synergistically with IH as a priming and activation signal of NLRP3 that enhances the inflammatory response, pyroptosis and TF release. Conclusions OSA patients with eSA exhibit NLRP3 activation by IH and the presence of oxLDL capable of releasing TF, constituting a pathway for the interaction between dyslipidaemia and systemic inflammation in the development of atherosclerotic lesions.
Management of Acute Uncomplicated Appendicitis
Authors: David A. Talan, Paulina Salminen
Journal: JAMA Surgery (2022)

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Error in Nonauthor Collaborators List
Journal: JAMA Network Open (2022)

Terence J. O’Brien, MD; Samuel F. Berkovic, MD; Jacqueline A. French, MD; John A. Messenheimer, MD; Terri B. Sebree, BS; Marcel O. Bonn-Miller, PhD; Donna L. Gutterman, PharmD; STAR 1/STAR 2 Study Group; Manori Wijayath; Peter Patrikios; David Reutens; Joseph Frasca ; Udaya Seneviratne; Wendyl D’Souza ; Peter Bergin; Tim Anderson; Ian Rosemergy; Armin Nikpour ; Patrick Kwan; Fredrik Asztely ; Ernest Somerville